Introduction to GMP Outsourcing and the Role of a Contract Development and Manufacturing Organization (CDMO)
Auditing is an essential task in ensuring quality assurance of a GMP Contract Development and Manufacturing Organization (CDMO). A customer makes a big decision when selecting a CDMO to manufacture its drug product. Time, money and reputations are committed with this decision. CDMO errors can lead to unforeseen market delays and production costs, which directly affect the company’s profitability. This is an important decision, and the audit is just one part of the total evaluation of the CDMO.
A CDMO provides contract development and manufacturing services to multiple companies. The relationship history and the complexity of the outsourced services are factors in determining the scope and approach to auditing. The trigger for an audit may be linked to a new relationship, the transition from a clinical fill (investigational product) to a contemplated commercial supplier contract, or it may be driven by deviations, complaints, or changes at the CDMO.
Why Audits Are Essential for Quality Assurance
Customers must understand what a CDMO does and believe what the CDMO claims it will do. Only then will an auditor report positively to management. Audits serve as a critical mechanism to verify regulatory compliance and assess the CDMO’s commitment to quality systems.
Every customer should define a procedure for when a CDMO receives a critical or major deficiency. If you are serious enough to issue a critical or major deficiency, you should address the potential impact on your own processes and products. Actions should include curtailing purchases from the CDMO, followed by a quality and risk assessment of existing lots of material on the market since the last acceptable audit was performed.
Auditors want a thorough understanding of the CDMO’s processes, systems, and weaknesses to satisfy themselves with the level of commitment to compliance. Astute auditors will quickly know if the correct quality systems are established and followed.
Dual Benefits: Advantages for Both CDMOs and Customers
Ideally, an audit benefits both the customer (auditor) and the CDMO (host) as regulatory compliance generally increases. A successful initial audit elevates a new CDMO to an “approved supplier,” allowing the CDMO to more easily pursue other services throughout the customer’s organization.
Auditors can serve as ambassadors to enhance the relationship by identifying improvements for both parties rather than solely finding fault. This open relationship rarely develops during the primary audit but emerges as the parties find mutual respect through repeated interactions.
Key Objectives of a Successful Audit
The primary objectives of a successful CDMO audit include:
Verification of Quality Systems: The auditor needs to verify that the CDMO has established and follows appropriate quality systems. From the organization chart, the auditor can estimate the percent of the CDMO personnel in the quality groups and the reporting structure. A quick scan of the SOP titles will signal the quality system’s adequacy. What is the frequency of critical SOP revisions? Does the quality system have written procedures, numbered records, and issuance logs for deviations, change orders, and out-of-specification reports? Are there internal audit and training programs? These are essential components of a functioning quality system.
Assessment of Regulatory Compliance: The auditor must confirm that the CDMO maintains compliance with applicable regulatory standards (e.g., 21 CFR Part 211, EU Guide to GMP). Before the auditor’s arrival, a conversation may dispel potential confusion about compliance expectations. The CDMO should be prepared to demonstrate compliance with the specific regulatory frameworks that apply to the customer’s products.
Evaluation of Risk Management: The customer faces difficult questions about the product or services if critical or major issues are identified. The auditor must assess the CDMO’s ability to identify, manage, and mitigate risks to product quality and patient safety. This includes reviewing the CDMO’s approach to change control, deviation management, and corrective and preventive actions (CAPA).
Building Confidence in the Relationship: Ultimately, audits are about knowledge and confidence. Experience helps everyone breeze through the agenda with enthusiasm. Experienced auditor and host teams build confidence in each other when they quickly work through issues and move on. The relationship develops as the parties find mutual respect through repeated interactions.
Establishing Clear Communication: Communication is key to audit success. The auditor needs to review the CDMO history before coming on site. This data should include previous customer audit reports, responses, and any complaints. Both parties should be prepared to cite regulations to support their position. That is why it is essential to monitor the FDA website for recent 483 observations, Warning Letters, and Guidance documents.
Critical Success Factors
Difficulties arise when the CDMO’s standard of performance and motivations collide with the customer’s expectations. We will discuss the typical audit process and identify critical elements for success throughout this guide. The appropriate choice of a host team facilitates a successful audit and develops staff for future audits and regulatory inspections. Similarly, the customer should assemble an audit team with the right expertise and approach to ensure a productive engagement.
Financial factors may ultimately affect everyone’s ambition toward meeting each other’s expectations. As always, the larger the financial stakes and the fewer the alternatives, the more interest each party has in accommodating one another. Notwithstanding, the CDMO needs to maintain their quality system, and the auditor needs to have confidence that the quality system is sufficient to pass regulatory scrutiny and ensure safe and effective product meeting patient requirements.
Remember, if all goes well, you get to see each other in two years!
